Postoperative Serum NLRP1 as a Biochemical Predictor of Delirium and Cognitive Decline After Hip Fracture Surgery in Elderly Patients: A Single Center Observational Study

Abstract

Objective: Postoperative delirium (POD) and cognitive decline (POCD) are linked to inflammatory brain injury, and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 1 (NLRP1) participates in neuroinflammation. Here, we investigated influential factors of serum NLRP1 levels and its predictive significance on POD and POCD of elderly patients with hip fracture. Materials and Methods: In this observational analytical study, serum NLRP1 levels were quantified in 100 controls, and preoperatively and postoperatively in 271 elderly patients undergoing hip fracture surgery. Primary outcome was postoperative three-month POCD [Montreal cognitive assessment (MoCA) scores below 26], and secondary outcomes included in-hospital POD and serum NLRP1 levels. The associations with them were analyzed using multivariate methods. Results: Compared to controls, patients had markedly heightened postoperative, but not preoperative, serum NLRP1 levels. Postoperative serum NLRP1 levels were independently associated with postoperative C-reactive protein levels and FRAIL scores. Postoperative serum NLRP1 and FRAIL scale scores were independently associated with POD, and together with POD, were also independently related to the MoCA scores and effectively predicted POCD. The results of the regression analyses were comparatively robust based on collinearity evaluation, sensitivity analysis, subgroup analysis, interactivity investigation, and restricted cubic spline analysis. The independent predictors of POD and POCD were integrated separately to form the respective models. The models were graphically delineated via nomograms and were efficaciously used to distinguish the risk of POD or POCD based on the calibration, decision, and receiver operating characteristic curves. By applying mediation analysis, POD may partially mediate the association between the postoperative serum NLRP1 levels and POCD. Conclusion: Serum NLRP1 may be a potential predictor of POD and POCD in elderly patients undergoing hip fracture surgery and the combined use of FRAIL and NLRP1 may optimize the efficiency of screening in high-risk populations.